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Polymorphism of XRCC1 and the frequency of mutation in codon 249 of the p 53 gene in hepatocellular carcinoma among guangxi population, China
Author(s) -
Long Xi Dai,
Ma Yun,
Huang Hong Dong,
Yao Jin Guang,
Qu De Ying,
Lu Yun Long
Publication year - 2008
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20384
Subject(s) - xrcc1 , biology , genotype , genetics , hepatocellular carcinoma , gene , microbiology and biotechnology , dna repair , single nucleotide polymorphism
In hepatocellular carcinoma (HCC), hotspot mutation in codon 249 of the p 53 gene has been associated with exposure to aflatoxin B1 (AFB1). While the polymorphism of DNA repair gene X‐ray repair cross‐complementary group 1 (XRCC1) Arg399Gln may be related with AFB1‐DNA adducts and gene mutations. Five hundred one HCCs were included in this study to investigate the role of the XRCC1 codon 399 polymorphism on hotspot mutation in codon 249 of the p 53 gene. The genotypes of XRCC1 codon 399 and p 53 codon 249 were examined by PCR‐RFLP. The HCC patients with XRCC1 genotypes with 399 Gln (namely: XRCC1‐AG/GG) exhibited a significantly higher frequency of the p 53 hotspot mutations in codon 249 than those with the wild‐type homozygote of XRCC1 [namely: XRCC1‐AA, adjusted odds ratio (OR) = 6.77, 95% confidence interval (CI) = 4.34–10.57]. Compared with those individuals who did express XRCC1‐AA as reference (OR = 1), moreover, individuals featuring XRCC1‐AG/GG and AFB1‐DNA adducts did experience a significantly greater frequency of the hotspot mutation in codon 249 of the p 53 gene (adjusted OR = 28.37, 95% CI = 13.19–61.02, P < 0.01). This study suggests that the XRCC1 Arg399Gln polymorphism and AFB1‐DNA adducts are associated with the increased frequency of the p 53 mutations in codon 249. © 2007 Wiley‐Liss, Inc.